Flu viruses mix it up

A map of the evolution of flu viruses has revealed just how frequently they swap genes with each other.

The result renews fears that a nasty virus such as avian influenza could pick up a gene from a human flu virus that makes it more transmissible, leading to a possible pandemic. And it highlights how easy it is for a strain of flu to evolve for which we don't have a vaccine.

The most serious causes of human flu, called A viruses, have the ability to swap genes when they infect the same person. This reassortment can produce strains that are more problematic because they differ from the ones our immune systems have learnt to recognize.

To investigate how often this happens, researchers looked at the published genome sequences of 156 flu strains that circulated in New York state between 1999 and 2004.

Swap shop

They constructed family trees that show how these viruses slowly evolved over time. And they discovered at least four instances where a virus had picked up a gene from another virus through reassortment. Edward Holmes, a biologist at the Centre for Infectious Disease Dynamics at Pennsylvania State University, University Park, and colleagues report the results in PLoS Biology1.

In one of these instances the gene swap resulted in a particularly nasty strain that struck New York in the winter of 2003-04. This 'Fujian' strain was produced when a virus that was common the previous year picked up a gene from a relatively harmless strain, which had been around for some years but infected very few people.

The gene was for a protein that the virus uses to bind to cells it is going to infect. The version the dominant strain picked up was very different to the one it had before, catching people's immune systems, and vaccines, unawares.

The researchers say they found a wider variety of strains circulating at any one time than expected, and more instances of gene swapping.

"Multiple lineages coexist at the same time and place, and the key thing is that they are reassorting and doing so quite frequently," says Holmes.

Clearer picture

Alan Hay, director of the World Health Organization's UK flu centre says the work will "give us a better idea of the variation and extent of recombination".

Hay adds that flu researchers already had a good idea of how reassortment happens, from studies that tracked specific genes for surface proteins. But Holmes's research goes beyond this by using whole genome sequences, he says, giving a clearer picture of how often this happens.

"I think these analyses will help us understand in detail the evolution of the influenza virus, taking into account more than just these genes," Hay says.

Holmes says that further studies investigating the genome sequences of bird-flu viruses could help us understand whether recombination is as just common in those.

Some researchers are now trying to create recombinant strains in the lab, using bird and human viruses, to see what a pandemic virus might look like and how easily it might form.